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Review Article

A structured approach to the assessment of a

floppy neonate
Molla Imaduddin Ahmed, Mehtab Iqbal, Nahin Hussain
Department of Paediatrics, Leicester Royal Infirmary, University Hospitals of Leicester, Leicester, United Kingdom

Address for correspondence: Dr. Molla Imaduddin Ahmed, Leicester Royal Infirmary, University Hospitals of Leicester, Infirmary Square,
Leicester, LE1 5WW, United Kingdom. E‑mail: drahmed38@gmail.com

ABSTRACT
Hypotonia in a newborn presents a diagnostic challenge for clinicians. It is an important clinical feature that
may indicate an underlying systemic illness or neurological problem at the level of the central or peripheral
nervous system. It is important to know the different presentations of hypotonia and to have the knowledge of
the diagnostic work up which requires multidisciplinary assessment and input and the prognostic implications of
these disorders. This review article presents a structured approach highlighting initial assessment, examination,
and management of a neonate with generalized hypotonia.

Key words: Floppy neonate, hypotonia, structured approach

Introduction Important Aspects in History and

Hypotonia in a newborn poses a diagnostic challenge
for neonatologists and pediatricians, as it is a clinical
sign suggestive of both benign and serious conditions.
The differential diagnosis for neonatal hypotonia is
extensive and a methodical approach helps in localizing
the problem to a specific region of the nervous system
and formulating a differential diagnosis. Most of these
neonates need prolonged mechanical ventilation, and
diagnosing the underlying cause helps plan the management
and inform the parents about the prognosis. This review
article presents a structured approach highlighting initial
assessment, examination, and management of a neonate
with generalized hypotonia.
Examination
Prenatal, neonatal, and perinatal history
The list of differential diagnosis of hypotonia in neonates is long,
but a good history will narrow the possibilities. A detailed family
history may be very helpful: A family history of neuromuscular
disease needs to be elicited; a history of repeated abortions
may suggest a variety of disorders with prenatal onset,
developmental delay (a chromosomal abnormality), delayed
motor milestones (a congenital myopathy), and premature
death (metabolic or muscle disease).[1]
Details of pregnancy, delivery, and postnatal period are
important. Prenatal risk factors include parental age,

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DOI:
10.4103/1817-1745.181250 Cite this article as: Ahmed MI, Iqbal M, Hussain N. A structured approach
to the assessment of a floppy neonate. J Pediatr Neurosci 2016;11:2-6.

2 / © 2016 Journal of Pediatric Neurosciences | Published by Wolters Kluwer - Medknow

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Ahmed, et al.: Assessment of a floppy neonate

consanguinity, a history of drug or teratogen exposure,
maternal diseases (diabetes/epilepsy), reduced fetal
movements, polyhydramnios, and breech presentation.
History of congenital infections ‑ toxoplasmosis, rubella,
cytomegalovirus, herpes simplex, and any history of pre‑ or
post‑natal insult increase the likelihood of central nervous
system (CNS) dysfunction as the underlying cause of
hypotonia.[2] It is also important to evaluate the mother for
muscle weakness and myotonia.[3]
Meticulous documentation of any delivery complications,
perinatal birth trauma, low Apgar scores, and time of onset
of the hypotonia should be done. A detailed history regarding
the degree of weakness and its progression should be recorded.
An abnormal fetal presentation and a shortened umbilical
cord indicate poor fetal movement and may point toward
neuromuscular disorder.[2] Neonates who need mechanical
ventilation soon after birth have significant muscle weakness.
Inborn error of metabolism should be considered in neonates
who are born with normal pregnancy and delivery who later
on develop hypotonia after a period of normality.[4]
hypotonia and examining mother may reveal the features of
myotonia. Likewise, neonatal myasthenia may be suspected
if mother displays fatigability of eyelids on upward gaze and
fatigability of arms with sustained forward extension.[1]
The major task in the evaluation of a hypotonic neonate is
to determine the anatomic level of the pathology; whether
it is central or peripheral in origin. The pattern of weakness
and muscle involvement may help to localize the involved
region in the nervous system [Table 1].
Clinical Features of Central Hypotonia
These hypotonic neonates show signs of abnormal
consciousness, seizures, apneas, abnormal posturing, and
feeding difficulties. Muscle power is relatively preserved and
axial weakness is a significant clinical feature. The tendon
reflexes are normal or hyperactive, and there is no evidence
of muscle fasciculations.[10] Diminished or absent tendon
reflexes point toward lower motor neuron lesion and brisk
reflexes indicate CNS dysfunctions.[1]

Tight fisting of the hands, which do not open spontaneously,

Clinical examination and in which the thumbs are enclosed by the other fingers
Clinical examination is the key in narrowing the differential or adducted across the palmar surface, and adduction of
diagnosis. The physical examination should include the the thighs such that the legs are crossed when the infant is
assessment of relevant clinical signs including a detailed held in vertical suspension (scissoring) may be evidence of
neurologic evaluation and an assessment for dysmorphic spasticity.[11]
features.[5,6] The presence of congenital malformations in
other organ systems and dysmorphic features indicates a Postural reflexes are generally preserved in infants with cerebral
possible syndromic diagnosis. Important conditions to rule hypotonia despite a paucity of spontaneous movements. In
out are trisomy 21 where hypotonia is associated with short some acute encephalopathies, the Moro reflex may be
stature,[7] characteristic facies and cardiac anomalies,[8] and exaggerated.[11]
Prader–Willi syndrome where hypotonia is associated with
characteristic facial features, reduced deep tendon reflexes,
Table 1: Differentiating the features of a floppy
feeding difficulties, and hypogonadism.[9] neonate according to the site of involvement[2,11]
Site of Clinical features Differential diagnoses
It is important to determine whether the baby has low tone involvement
with or without weakness. Tone is defined as resistance of Central Central hypotonia Brain malformations
muscle to stretch, therefore babies with hypotonia have Brisk or normal tendon Perinatal asphyxia
decreased resistance on passive stretching.[5] On the other reflexes Chromosomal disorders
hand, weakness is decreased muscle strength or power.[6] Lack Preserved neonatal Inborn errors of
reflexes metabolism
of spontaneous movement in a baby suggests weakness. Most Abnormal brain function
hypotonic neonates demonstrate a characteristic frog‑legged Anterior horn Generalized weakness Spinomuscular atrophy
posture‑full abduction and external rotation of the legs as well cell and absent deep
as a flaccid extension of the arms.[1] Other signs of hypotonia tendon reflexes
include head lag, slip‑through on vertical suspension, and Nerve Distal muscle weakness Peripheral neuropathy
and wasting
draping on ventral suspension. Decreased tendon
reflexes
Weakness can be assessed by the cry, facial expressions, Neuromuscular Involvement of facial Myasthenia gravis
sucking and Moro’s reflex, antigravity movements, and junction muscles with or without botulism
respiratory effort. It is important to evaluate the distribution generalized weakness
Muscle Weakness Congenital muscular
and progression of weakness in differentiating the causes of Decreased tendon dystrophy
neonatal hypotonia. reflexes Congenital myotonic
Fasciculations joint dystrophy
Physical examination of parents may also provide useful cues contractures Congenital and
as babies with congenital myotonic dystrophy have severe metabolic myopathy

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Ahmed, et al.: Assessment of a floppy neonate
Clinical Features of Peripheral
Hypotonia
Babies with anterior horn cell disease usually have sparing of
extra‑ocular muscles while the disorders of neuromuscular
junctions may have ptosis and extra‑ocular muscle
weakness.[6] These infants appear more alert in comparison
to those with CNS involvement. There is weakness in
the antigravity limb muscles along with diminished or
absent reflexes. They can have deformities of bones or
joints (arthrogryposis).[2] Fasciculations, often observed in
the tongue, are often very difficult to distinguish from normal
random tongue movements. Postural reflexes are absent or
diminished, and limbs that lack voluntary movement also
cannot move reflexively.
Investigations
Appropriate use of investigations is necessary to establish a
specific etiologic diagnosis and should be guided by the history
and physical examination. We suggest a systematic approach
based on the tests currently utilized in the evaluation of infants
with hypotonia. Clinical details and relevant diagnostic tests
are discussed in conjunction with specific disorders.
Here is a list of investigations for neonates with hypotonia
(a schematic approach to the diagnosis of neonatal hypotonia
is shown in Figure 1).
Neuroimaging
In babies with features of central hypotonia, neuroimaging is
a valuable tool for diagnosis. Cranial and spinal neuroimaging
(computed tomography/magnetic resonance imaging) studies
are helpful in the identification of structural malformations,
neuronal migration defects, brain stem and cerebellar
abnormalities, and can identify features suggestive of
mitochondrial abnormalities and metabolic diseases.
Genetic studies
These tests should be chosen according to the clinical
presentation of the infants. The karyotype will disclose any
genetic defects such as chromosomal duplications, deletions,
trisomies such as Down syndrome (Trisomy 21), and disorders
of genetic imprinting such as Prader Willi syndrome.
Molecular genetic tests may also help in the diagnosis of spinal
muscular atrophy (SMA) (deletion of SMN gene)[12,13] and
myotonic dystrophy (trinucleotide repeats).[14]
Blood investigations
Blood investigations including full blood count, electrolytes,
and inflammatory markers are important to rule out
systemic disorders causing hypotonia including sepsis and
dyselectrolytemias. Muscle enzymes (creatine kinase [CK]
assay) are helpful in diagnosing muscle disorders such as
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congenital muscular dystrophies, metabolic myopathies,
and some forms of the congenital myopathies. The blood
for CK measurement should be obtained before performing
the electromyography or muscle biopsy, as these procedures
may cause false elevation of CK levels. The CK and
iso‑enzyme levels may be increased 10‑fold for up to 1 week
following normal vaginal delivery (presumably due to muscle
trauma). The CK may be even higher in the context of
acidosis (e.g., severely asphyxiated newborns). [11] Other
biochemical investigations (e.g., serum lactate and carnitine
levels) may be required in specific circumstances.
Chest X‑ray
A chest radiograph may demonstrate enlarged cardiac
shadows indicating cardiomyopathy or thin ribs, related to
reduced fetal respiratory movements. The latter observation
is a useful clue to antenatal onset of neuromuscular disease.
An enlarged heart on chest X‑ray may suggest Pompe disease.
Lumbar puncture
Cerebrospinal fluid (CSF) analysis is important to rule out
neuroinfections. Markedly, increased protein concentration
in CSF may indicate peripheral neuropathy or specific
degenerative conditions.
Screening for inborn errors of metabolism
If the clinical picture suggests multisystem involvement,
screening should be done for inborn errors of metabolism.[4]
Electrophysiological studies
Nerve conduction and electromyogram studies are useful
in the assessment of disorders affecting the lower motor
unit. Electromyography[15] is very helpful in establishing
the diagnosis of SMA and disorders of the neuromuscular
junction (botulism and congenital forms of myasthenia
gravis).
Nerve conduction studies are consistent and reliable after
32 weeks of gestation. [11] Nerve conduction velocities
may be very slow or unrecordable in congenital peripheral
neuropathies. Nerve conduction studies and electromyography
are also useful in diagnosing hereditary motor sensory
neuropathies and in differentiating axonal disorders from
demyelinating conditions. [16,17] Slow nerve conduction
velocity and conduction block favor peripheral nerve
involvement.
Muscle and nerve biopsies
These investigations should be considered, even if the
electrophysiological studies are normal.[18] Muscle biopsy
with immunohistochemical staining and electron microscopy
is the method of choice for differentiating myopathies and
muscular dystrophies, although it is more invasive. If biopsy
shows specific abnormalities, it can be an essential part of the
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Ahmed, et al.: Assessment of a floppy neonate

Floppy neonate

History and physical examination

Hypotonia with abnormal consciousness, seizures, Hypotonia, weakness, alert look, fasciculations,
apnea, abnormal posturing, and feeding difficulties absent or reduced tendon reflexes

Muscle weakness in mother

CT/MRI, Screening for IEM, Septic screen,
CSF analysis, Karyotype
Yes

No Maternal myotonia
Perinatal asphyxia, cerebral malformations, IEM,
sepsis, chromosomal disorders
Yes No

Myotonic History of
Creatine kinase dystrophy myasthenia
in mother

High Normal

Congenital DNA testing for spinal

muscular muscular atrophy (SMN) Yes SMA
dystrophy Transient
Negative myasthenia
gravis – AchR
Ab and
EMG and NCS edrophonium
test

Myopathic Neuropathic Neuromuscular transmission defect

NCV
Congenital Transient myasthenia gravis,
myopathies Reduced congenital myasthenia syndromes
Normal
Peripheral
Neuropathy
Confirm by SMA
muscle biopsy
Confirm by
nerve biopsy

Figure 1: Evaluation of a neonate with generalized hypotonia.[2,5,10,19] CT: Computed tomography, MRI: Magnetic resonance imaging, IEM: Inborn errors of
metabolism, CSF: Cerebrospinal fluid, NCV: Nerve conduction velocity, SMA: Spinal muscular atrophy, NCS: Nerve conduction study

diagnostic evaluation in the newborn to guide subsequent
DNA molecular diagnostic studies.
What is the Management of this Clinical
Presentation?
Hypotonia is an important clinical presentation at birth or in
the first few days of life. A specific diagnosis can help tailor
the management and explain the prognosis to parents.
It is very important to continue supportive care with
regards to feeding and respiration. Most of these hypotonic
neonates need prolonged mechanical ventilation. Regular
physiotherapy is needed to aid the clearance of respiratory
secretions and will prevent limb contractures. It is vital to
aggressively treat any respiratory infections. Feeding should
be initiated by nasogastric tube and gastrostomy may be
needed for few babies. Weight should be closely monitored as
excessive weight gain can worsen existing muscle weakness.
Children with neuromuscular disorders need attention if they
require anesthesia. Muscle relaxants should only be used
if necessary as they have a more prolonged effect in these
children. They are also susceptible to malignant hyperthermia
and implicating agents should be avoided.[20]

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Ahmed, et al.: Assessment of a floppy neonate
It is important to ensure multidisciplinary follow‑up for
neonates with neuromuscular disorders. Follow‑up should
be arranged with neurologist and respiratory team, and an
appointment with the geneticist for genetic counseling should
be offered.
If there are symptoms and signs of severe neuromuscular
involvement at birth (with respiratory insufficiency, lack
of swallowing, cough, and tendon reflexes), the prognosis
is very poor. Such a presentation should lead to timely
ethical discussions as well as parental counseling and to the
consideration of early extubation. In babies with hypotonia
who survive the neonatal period, it is important to have
detailed discussions sensitively with parents regarding the
appropriateness of cardiopulmonary resuscitation in the event
of cardiac arrest or acute respiratory failure.
Conclusion
The list of differential diagnoses for floppiness in the neonatal
age group is extensive. However, most of these neonates
have distinctive features in their family history, history at
presentation, and their physical examination that can help
differentiate them into central and peripheral disorders, and
sometimes can lead to specific diagnoses within these groups.
As there are frequent implications for future pregnancies, and
specific treatments are available in a few disorders, we should
strive for an accurate diagnosis in these neonates.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Leyenaar J, Camfield P, Camfield C. A schematic approach to hypotonia
in infancy. Paediatr Child Health 2005;10:397‑400.
6 / Journal of Pediatric Neurosciences / Volume 11 / Jan-Mar / 2016
2. Prasad AN, Prasad C. The floppy infant: Contribution of genetic and
metabolic disorders. Brain Dev 2003;25:457‑76.
3. Dubowitz V, editor. The floppy infant syndrome. In: Muscle Disorders in
Childhood. 2nd ed. London: WB Saunders Company; 1995. p. 457‑72.
4. Tein I. Neonatal metabolic myopathies. Semin Perinatol 1999;23:125‑51.
5. Fenichel GM, editor. The hypotonic infant. In: Clinical Pediatric
Neurology: A Signs and Symptoms Approach. 4th ed. Philadelphia:
WB Saunders Company; 2001. p. 149‑69.
6. Crawford TO. Clinical evaluation of the floppy infant. Pediatr Ann
1992;21:348‑54.
7. Morris AF, Vaughan SE, Vaccaro P. Measurements of neuromuscular
tone and strength in Down’s syndrome children. J Ment Defic Res
1982;26(Pt 1):41‑6.
8. Rogers PT, Coleman M. Medical Care in Down Syndrome. New York:
Dekker; 1992.
9. Cassidy SB, Schwartz S, Miller JL, Driscoll DJ. Prader‑Willi syndrome.
Genet Med 2012;14:10‑26.
10. Paro‑Panjan D, Neubauer D. Congenital hypotonia: Is there an
algorithm? J Child Neurol 2004;19:439‑42.
11. Hill A. Neonatal hypotonia. In: Maria BL, editor. Current Management
in Child Neurology. 3rd ed. Hamilton: B C Decker Inc.; 2005. p. 529‑34.
12. Vitali T, Sossi V, Tiziano F, Zappata S, Giuli A, Paravatou‑Petsotas M,
et al. Detection of the survival motor neuron (SMN) genes by FISH:
Further evidence for a role for SMN2 in the modulation of disease
severity in SMA patients. Hum Mol Genet 1999;8:2525‑32.
13. Lefebvre S, Bürglen L, Frézal J, Munnich A, Melki J. The role of the
SMN gene in proximal spinal muscular atrophy. Hum Mol Genet
1998;7:1531‑6.
14. Kamsteeg EJ, Kress W, Catalli C, Hertz JM, Witsch‑Baumgartner M,
Buckley MF, et al. Best practice guidelines and recommendations on the
molecular diagnosis of myotonic dystrophy types 1 and 2. Eur J Hum
Genet 2012;20:1203‑8.
15. David WS, Jones HR Jr. Electromyography and biopsy correlation with
suggested protocol for evaluation of the floppy infant. Muscle Nerve
1994;17:424‑30.
16. Renault F. The role of electrodiagnostic studies in the diagnosis of
hypotonia in infancy. Rev Med Liege 2004;59 Suppl 1:190‑7.
17. Russell JW, Afifi AK, Ross MA. Predictive value of electromyography
in diagnosis and prognosis of the hypotonic infant. J Child Neurol
1992;7:387‑91.
18. Richer LP, Shevell MI, Miller SP. Diagnostic profile of neonatal
hypotonia: An 11‑year study. Pediatr Neurol 2001;25:32‑7.
19. Hahn JS, Henry M, Hudgins L, Madan A. Congenital hypomyelination
neuropathy in a newborn infant: Unusual cause of diaphragmatic and
vocal cord paralyses. Pediatrics 2001;108:E95.
20. Wedel DJ. Malignant hyperthermia and neuromuscular disease.
Neuromuscul Disord 1992;2:157‑64.